Do new and old biomarkers of early undifferentiated arthritis correlate with Arthritis Impact Measurement Scales?

OBJECTIVES: In early undifferentiated arthritis (EUA), the relationship between inflammatory biomarkers and disability is still unclear. The aim of this study was to correlate inflammatory biomarkers with the Arthritis Impact Measurement Scales (AIMS) in EUA. METHODS: Seventy patients with EUA were compared with 20 patients with established rheumatoid arthritis (RA). The association of AIMS [mobility, physical impairment (PI), dexterity, household activities, activities of daily living (ADL), social activity, pain, anxiety, depression] with serum laboratory [phase acute reactants, calprotectin, interleukin-6, tumour necrosis factor (TNF)-α, rheumatoid factor, anti-nuclear and anti-citrullinated peptide antibodies, HLA-DRB], clinical [Clinical Disease Activity Index (CDAI), fatigue, pain and stiffness NRS], x-ray and ultrasound biomarkers was analysed with non-parametric Spearman's rank correlation and Mann-Whitney U tests. RESULTS: No differences in AIMS were found between EUA and established RA patients, or between EUA patients that evolved into early RA (n=17) and those that remained EUA (n=53) at six months of follow-up. In EUA, erythrocyte sedimentation rate correlated with mobility impairment, PI and depression (p=0.04, p=0.03 and p=0.022, respectively), TNF-α correlated with PI (p=0.01) and calprotectin with anxiety (p=0.02). HLA-DRB1*11-positive EUA patients had lower ADL deficiency (p=0.006), depression (p=0.0004) and anxiety (p=0.01). CDAI correlated with PI (p=0.01) and pain (p=0.01), fatigue with PI (p=0.0001) and ADL (p=0.009), stiffness with PI (p=0.01), and Power Doppler ultrasound synovitis with PI (p=0.02) and pain (p=0.007). CONCLUSIONS: In EUA, physical and mood disorders are associated with new and old inflammatory serological, clinical and imaging biomarkers. HLA-DRB1*11-positivity may be protective against these disease-related features.

Two Novel Technologies for the Detection of Anti-cardiolipin and Anti ß2-Glycoprotein Antibodies in the Real Life: Chemiluminescent in Comparison to the Addressable Laser Bead Immunoassays.

In the present study, we evaluated two novel technologies, the chemiluminescent immunoassay (CIA) QUANTA Flash on BIO-FLASH (Inova Diagnostics, San Diego, CA, USA) and the addressable laser bead immunoassay (ALBIA) on BioPlex™ 2200 (Bio-Rad, Hercules, CA, USA) for the detection of anti-cardiolipin IgG/IgM (aCL) and anti-ß2-glycoprotein IgG/IgM (aß2GPI) antibodies. The study was performed on 134 samples from consecutive patients (59 males and 75 females, mean age 54 ± 10 years) who consulted a rheumatologist because thrombosis and/or pregnancy complications were present or another immunological disease (Sjogren's syndrome, inflammatory arthritis). Fourteen patients of the total fulfilled 25the Sydney criteria for APS and for these patients previous results of aPLs were available. Sera were tested for aCL and aß2GPI of IgG and IgM isotypes using CIA (BIO-FLASH) and ALBIA (BioPlex™ 2200). Overall agreement between CIA and ALBIA ranged from 88.1% (aCL IgG) to 97.8% (aß2GPI IgG). Cohen's kappa coefficient ranged from 0.53 to 0.91, implying moderate to almost perfect agreement. Almost perfect agreement was found between BioPlex™ 2200 and BIO-FLASH aß2GPI IgG and aCL IgM with Cohen's kappa of 0.91 and 0.88, respectively. On the other hand, moderate agreement was found between BioPlex™ 2200 and BIO-FLASH aCL IgG and ß2GPI IgM assays with Cohen's kappa of 0.57 and 0.53, respectively. The two novel technologies look promising and comparable but further studies with larger cohorts are needed to contribute to the better understanding of the new aPLs antibodies assays performance.

Tocilizumab modulates serum levels of adiponectin and chemerin in patients with rheumatoid arthritis: potential cardiovascular protective role of IL-6 inhibition.

OBJECTIVES: Adipokines play an important role in the pathophysiology of rheumatoid arthritis (RA), provide a link between the disease and overweight, contributing to explain the enhanced cardiovascular (CV) risk and influence the response to disease-modifying anti-rheumatic drugs. The aim of this study was to determine the possible effects of intravenous (IV) tocilizumab (TCZ), an interleukin-6 receptor antagonist, on serum levels of leptin, adiponectin, resistin, visfatin, and chemerin. METHODS: Forty-four RA patients with active disease (DAS28-ESR ≥3.2) were treated with IV TCZ (8 mg/kg) once every 4 weeks for six months: 20 patients received TCZ as monotherapy and 24 in association with methotrexate (MTX). At baseline and monthly, before each infusion, body mass index, DAS28-ESR and Health Assessment Questionnaire (HAQ) were recorded. The laboratory parameters, including the adipokines serum levels were collected at baseline and after six months. RESULTS: At the end of the follow-up, ESR, CRP, DAS28-ESR and HAQ resulted significantly improved in patients received TCZ as monotherapy or combined with MTX. Lipid profile showed only a significant increase of total cholesterol. A significant reduction of chemerin and an increase of adiponectin were observed in the whole population and in the subgroups of the patients analysed (TCZ mono or combined therapy) without any significant correlations with clinical and biochemical parameters. No changes in the leptin and resistin levels were detected. CONCLUSIONS: TCZ is able to regulate serum levels of chemerin and adiponectin in RA patients, independently of the disease treatment response, which contributes to explain the CV safety of TCZ.

Anti-DFS70 autoantibodies in undifferentiated connective tissue diseases subjects: what's on the horizon?

OBJECTIVE: The main objective was to determine the prevalence of anti-dense fine speckled (DFS70) antibodies in a stable population of undifferentiated connective tissue disease (UCTD) to better define their potential role. METHODS: Immunological and clinical records of 91 long-standing UCTD patients were studied. DFS pattern was determined using the IIF ANA test on HEp-2 cells and anti-DFS70 antibodies were tested by chemiluminescence assay and by DFS70 line immunoassay. RESULTS: Twelve (13.2%) of 91 serum samples were positive for anti-DFS70 antibodies by chemiluminescence assay and line immunoassay. There was no statistical significance between the prevalence of anti-ENA and anti-DNA autoantibodies in patients with and without anti-DFS70 antibodies. No differences were found in the clinical characteristics of both groups. The presence of the anti-DFS70 antibodies was related to the younger age class. CONCLUSION: The high prevalence of anti-DFS70 antibodies in the UCTD patients suggested the potential role of these autoantibodies as a marker in the evolution of UCTD to CTD.

Musculoskeletal ultrasonography for psoriatic arthritis and psoriasis patients: a systematic literature review.

Objective: To systematically review the role of musculoskeletal US in patients suffering from PsA or psoriasis (Pso) in terms of prevalence, diagnosis, prognosis, monitoring and treatment. Methods: A systematic literature review was conducted through medical databases (MEDLINE via PubMed, Embase) and the grey literature up to September 2015 to inform a new study of the Musculoskeletal Ultrasound Study Group of the Italian Society for Rheumatology. All articles reporting data on musculoskeletal US in PsA or Pso were included and extracted according to the underlying clinical question. Results: A total of 86 publications were included. The prevalence of US abnormalities showed a wide range for each examined feature (e.g. 37-95% for entheses thickness of the lower limbs). The performance of US for diagnosis of disease or elementary lesions was variable across studies, but no study evaluated the overall performance of US in addition to clinical findings for diagnosing PsA. Considering US in defining PsA and Pso prognosis, several works focused on US of entheses of lower limbs in Pso, while for the monitoring of PsA activity five different scoring systems were identified. Last, the results of the role of US in guiding intra-articular interventions were controversial for the clinical outcomes, but in favour of US for accuracy. Conclusion: despite the recognized importance of US in the management of PsA and Pso, this review clearly demonstrated the need of pivotal research in order to optimize the use of US in the diagnosis and monitoring of psoriatic disease.

Ultrasonographic wrist and hand abnormalities in early psoriatic arthritis patients: correlation with clinical, dermatological, serological and genetic indices.

OBJECTIVES: The aims of our study are to describe the wrist and hand ultrasound (US) abnormalities compared to clinical examination in early psoriatic arthritis (ePsA) and to analyse their correlation with clinical, dermatological, serological and genetic indices. METHODS: We analysed 1120 fingers and 224 wrists of 112 early PsA, with MyLab70 Xview (Esaote, linear probe) ultrasound (US). Power Doppler active synovitis (AS), erosions, finger tendons tenosynovitis or peritendinitis (TP) and pseudotenosynovitis (PT), were compared to clinical (BASDAI, SHAQ), dermatological (PASI and psoriasis aspects), serological (ESR, CRP, ACPA) and genetic (HLA haplotypes) indices. RESULTS: All US abnormalities were present: AS was more frequent at wrists (50/224 [22.3%]), followed by hand PT (68/1120 [6,1%]) and TS (29/1120 [2.6%]), while erosions were rare (10/1120 [0.8%]). US abnormalities were independent of ePsA clinical indices (except erosions - even if represented only in a low percentage - that correlated to BASDAI [p<0.05]), while they were associated to several dermatological (except PASI), serological and genetic parameters: psoriasis (all p<0.0001), palmoplantar psoriasis (wrist and hand AS p<0.0005 and p<0.005, respectively), hand psoriasis (all p<0.0001), nail dystrophy (hand AS p<0.05, PT p<0.0001, erosions p<0.0001); positive CRP (all p<0.0001), ESR (wrist and hand AS p<0.005 and <0.0005, respectively, TS, PT and erosions p<0.0001) and ACPA - even if represented only in 1.78% of patients - (wrist and hand AS and TS p<0.0001, PT p<0.5); HLA-B27 (wrist and hand AS p<0.0001, TS p<0.01, PT p<0.05), -B35 (wrist and hand AS p<0.01 and p<0.05, respectively), -B38 (wrist and hand AS p<0.0001, TS p<0.0001, PT p<0.005), -CW6 (wrist AS p<0.05), -DR4 (wrist and hand AS p<0.0001, TS p<0.0001, PT p<0.005). CONCLUSIONS: US abnormalities of hand and wrist were independent of clinical ePsA indices (except erosions), while they correlated to dermatological (except PASI), serological and genetic parameters of disease.

Lymphatic endothelial progenitor cells and vascular endothelial growth factor-C in spondyloarthritis and Crohn's disease: two overlapping diseases?

OBJECTIVES: The role of the lymphatic system in the connection between spondyloarthritis (SpA) and Crohn's disease (CD) remains yet to be elucidated. The aim of the present study was to investigate the circulating levels of lymphatic endothelial progenitor cells (LEPCs) and vascular endothelial growth factor-C (VEGF-C) and their possible correlation with clinical parameters in SpA, SpA associated with CD (SC), and CD. METHODS: Peripheral blood samples from SpA (n=36), SC (n=20) and CD (n=28) patients and 20 age- and sex-matched healthy controls were collected and used for quantification of circulating LEPCs and VEGF-C. LEPCs were identified by fluorescence-activated cell sorting using FITC-CD34, APC-CD133 and PE-VEGFR-3 antibodies. Serum levels of VEGF-C were measured by enzyme-linked immunosorbent assay. The possible correlations between disease duration (< or >10 years; < or >20 years) and clinical activity (BASDAI for SpA or CDAI for CD) and LEPC counts and VEGF-C levels were analysed. RESULTS: Circulating LEPC levels were significantly increased in SpA (p=0.0006) and SC (p=0.0058) patients compared with controls. In CD patients, LEPC counts negatively correlated with disease duration, with lower levels in longstanding disease (>20 years, p=0.018), but were not different from controls. No significant difference in VEGF-C levels was found in SpA, SC and CD compared with controls. Both LEPC and VEGF-C levels were independent of BASDAI and CDAI. CONCLUSIONS: On the basis of our observations, an active mobilisation of lymphatic endothelial cell precursors was observed only for spondylitis involvement.

Occult radiological sacroiliac abnormalities in patients with inflammatory bowel disease who do not present signs or symptoms of axial spondylitis.

OBJECTIVES: To investigate radiological sacroiliac abnormalities in IBD patients without musculoskeletal symptoms and to determine the clinical and familiar differences between IBD patients with and without radiologic sacroiliac joint (SIJ) abnormalities. Subsequently, the patients with x-ray alterations were followed for 3 years in order to assess the onset of chronic inflammatory back pain (IBP). METHODS: 81 patients (55 Crohn-CD- and 26 ulcerative rettocolitis-UC) with remittent and low active IBD, from a tertiary referral centre of Gastroenterology Unit, were studied using SIJ x-rays. Differences in IBD clinical variables (activity and duration of CD and UC, extra-intestinal involvement, treatment with surgery and not, ESR and CRP levels), familiarity (for psoriasis, IBD, spondyloarthritis, coeliac syndrome), between patients with SIJ x-ray findings and without were investigated. Patients with radiological sacroiliac joint abnormalities were followed up clinically for 3 years and the onset of symptoms of chronic (higher than 3 consecutive months) IBP was investigated. RESULTS: 22/81 patients (27.1%) showed radiological SIJ abnormalities at baseline: isolated sclerosis in 17/22 (77.3%) and localised erosions in 12/22 (54.5%). Radiological SIJ involvement did not correlate with IBD clinical and familial variables. All patients were HLA B27 negative. At 3 years, 4/22 patients (18.1%) presented chronic IBP symptoms with bone oedema at MRI. CONCLUSIONS: In IBD, occult radiological SIJ alterations might precede the onset of axial symptoms but, in the absence of clinical signs, it is not possible to identify some IBD features or familiar predisposition that might be more frequent when SIJ abnormalities are involved. Clinical follow-up might be useful in these patients for a diagnosis of axial spondyloarthritis onset.

Muscle shortening manoeuvre reduces pain and functional impairment in shoulder impingement syndrome: clinical and ultrasonographic evidence.

OBJECTIVES: To evaluate the short-term efficacy of muscle shortening manoeuvre (MSM), by inducing an increase in strength of the shoulder muscles, for the treatment of shoulder impingement syndrome (SIS). METHODS: Sixty subjects (mean age: 58.6 years) with SIS were assigned to one of 3 different treatment interventions: 1) MSM: a series of fast accelerations in the upward direction was applied to the upper limb that was also submitted to forces acting in the opposite direction (added mass); 2) traditional physiotherapeutic technique: scapulothoracic gliding; 3) simple traction: the added mass was applied to the limb without the series of fast accelerations. Pain intensity, Neer's impingement sign, range of motion and muscle strength were assessed. Ultrasound (US) examination was performed before, immediately after and 30 days after each treatment to study the width of the subacromial-subdeltoid bursa, long biceps tendon sheath and acromioclavicular joint. Impingement was evaluated by dynamic examination. RESULTS: After treatment with MSM, pain was significantly reduced (p<0.001), Neer's impingement sign was negative, range of motion and muscle strength were increased. US examination showed that the widths of the subacromial-subdeltoid bursa (p<0.001), long biceps tendon sheath (p<0.001) and acromioclavicular joint (p<0.001) were significantly reduced; impingement was no more detected. After 30 days, improvement in clinical and US findings was maintained. In the two control groups, no significant changes were observed after treatment. CONCLUSIONS: Clinical and US findings demonstrate that MSM, by inducing an increase in muscle strength, is effective in the short-term treatment of SIS.

Sex Bias in Diagnostic Delay: Are Axial Spondyloarthritis and Ankylosing Spondylitis Still Phantom Diseases in Women? A Systematic Review and Meta-Analysis.

Diagnostic delay (DD) is associated with poor radiological and quality of life outcomes in axial spondyloarthritis (ax-SpA) and ankylosing spondylitis (AS). The female (F) population is often misdiagnosed, as classification criteria were previously studied mostly in males (M). We conducted a systematic review to investigate (i) the difference in DD between the sexes, the impact of HLA*B27 and clinical and social factors (work and education) on this gap, and (ii) the possible influence of the year of publication (before and after the 2009 ASAS classification criteria), geographical region (Europe and Israel vs. extra-European countries), sample sources (mono-center vs. multi-center studies), and world bank (WB) economic class on DD in both sexes. We searched, in PubMed and Embase, studies that reported the mean or median DD or the statistical difference in DD between sexes, adding a manual search. Starting from 399 publications, we selected 26 studies (17 from PubMed and Embase, 9 from manual search) that were successively evaluated with the modified Newcastle-Ottawa Scale (m-NOS). The mean DD of 16 high-quality (m-NOS > 4/8) studies, pooled with random-effects meta-analysis, produces results higher in F (1.48, 95% CI 0.83-2.14, p < 0.0001) but with significant results at the second analysis only in articles published before the 2009 ASAS classification criteria (0.95, 95% CI 0.05-1.85, p < 0.0001) and in extra-European countries (3.16, 95% CI 2.11-4.22, p < 0.05). With limited evidence, some studies suggest that DD in F might be positively influenced by HLA*B27 positivity, peripheral involvement, and social factors.

Is Active Synovitis of Metacarpophalangeal Joints a Neuropathic Condition in Rheumatoid Arthritis Patients? Results from an Ultrasound Study of Palmar Digital Nerves.

(1) Background: Rheumatoid arthritis (RA) is a chronic inflammatory joint disease, primarily characterized by pain. A significant proportion of patients report symptoms suggestive of neuropathic pain. The objectives of this study were to investigate the presence of an increased cross-sectional area (CSA) of the palmar digital nerves by ultrasound in patients with active synovitis of the metacarpophalangeal joints and to identify potential predictors of such an increase. (2) Methods: An ultrasound examination of the clinically most affected hand (from the second to the fifth metacarpophalangeal joint) was performed. The presence of synovitis was scored using a 0-3 semiquantitative method for each joint. The CSA of each pair of palmar digital nerves was measured. (3) Results: A significant correlation was found between the sum of the CSAs of the nerves and the Clinical Disease Activity Index (CDAI) (r = 0.387), as well as with the ultrasonographic grading of synovitis (r = 0.381) both at the patient and the joint level. These two variables, aimed at measuring disease activity, along with male gender, are the only predictors of the CSA of the palmar digital nerves. (4) Conclusions: Synovial inflammation of the metacarpophalangeal joints is, therefore, a condition that can influence the CSA of the palmar digital nerves and may partially explain neuropathic pain in patients with RA.

Do Ultrasound Lung Abnormalities Correlate to Biomarkers and Male Gender in Rheumatoid Arthritis Patients? A Monocentric Cross-Sectional Study.

Background: Lung ultrasound (LUS) is a tool of growing interest in Rheumatoid Arthritis (RA) oligo- symptomatic ILD to avoid. Objective: We aimed to evaluate (i) the prevalence of pleural (PLUS) and parenchymal (PAUS) abnormalities in LUS in the RA population and their possible correlation to biomarkers; (ii) the predictivity of gender, smoking habits, previous infections (past COVID-19 tuberculosis), and treatments; (iii) the differences in LUS between sexes. Methods: We collected the data of 155 (15 early and 140 late) RA patients with mild respiratory symptoms, evaluating PLUS and PAUS, in fourteen lung areas and also summing the scores (LUS-T). Results: Only 13/155 (8.4%) were completely negative; LUS correlated to age (all parameters p 0.0001), rheumatoid factor IgM (PLUS p 0.0006, PAUS p 0.02, LUS-T p 0.001) and ACPA (p 0.001, 0.006, 0.001, respectively), and PLUS also correlated to IL6 (p 0.02). The male gender was predictive of all LUS evaluations (p 0.001, 0.05, 0.001, respectively), which were higher than in women (p 0.001, 0.01, 0.001, respectively). Other potential risk factors were independent, except biological treatments, which showed a low predictivity to PLUS (p < 0.05). Conclusions: We can conclude that LUS is a useful technique in RA low respiratory symptoms and correlates with age, the most important RA biomarkers, and male sex.

Clinical and radiological evaluation of sacroiliac joints compared with ultrasound examination in early spondyloarthritis.

OBJECTIVE: To compare clinical and X-ray examinations with US findings of SI joints (SIJ) in early SpA patients. METHODS: Twenty-three early SpA patients, diagnosed according to Assessment of SpondyloArthritis international Society criteria, were investigated clinically [sacral sulcus tenderness, BASMI, BASFI, BASDAI, pain and fatigue visual analogue scale (VAS), morning stiffness and sleep disturbance], with SIJ X-rays (New York score) and with My Lab70 US 7-10 MHz US (Esaote, Genoa, Italy), evaluating the width of the SIJ capsule and posterior sacroiliac (PSL) and sacrotuberosus (STL) ligament thickness and comparing the results with 23 healthy controls. RESULTS: SIJ width [right 2.2 (0.6) and left 2.3 (0.7) in SpA vs 1.6 (0.1) and 1.7 (0.2) in healthy controls, respectively, expressed as mean (s.d.)] and STL thickness [right 3.9 (1.3) and left 3.4 (1.0) vs 1.8 (0.1) and 1.8 (0.1), respectively, expressed as mean (s.d.)] were higher in SpA patients than in controls (P < 0.001 and P < 0.05, respectively). PSL thickness was similar in patients and controls. Only STL thickness was higher when SIJ was tender at clinical examination (P < 0.01) and correlated with pain VAS (P < 0.001) and BASFI (P < 0.05). Furthermore, SIJ US results were unrelated to X-ray findings (similar when X-ray sacroiliitis was present and not). CONCLUSION: Our exploratory study suggested that in early SpA patients US might be a promising method, complementary to other imaging techniques, to study articular and soft tissue periarticular involvement of SIJ, independent of clinical and X-ray examination.

Ultrasound-integrated tight control in early psoriatic arthritis during adalimumab treatment.

Psoriatic arthritis (PsA) is a multi-faceted disease, challenging the rheumatologist both for its complex diagnostic and therapeutic aspects. The efficacy of TNF-blockers treatment might be verified by the new imaging devices such as ultrasonography (US) that has a great impact on the tight control during follow-up. Otherwise, specific guidelines for the routine use of US in PsA are still not well defined and often the management of the disease is based only on the evidence-based experience of clinicians. In a young patient affected by early PsA, we describe the rapid and sustained remission of the disease after adalimumab treatment, accompanied by the healing of synovitis and erosion, underlining the importance of early aggressive therapy and the positive role of US tight control in the follow-up period.

Stiff skin syndrome and myeloma successfully treated with autologous haematopoietic stem cell transplantation (HSCT).

Stiff skin syndrome (SSS) is a rare scleroderma-like syndrome characterised by stone hard skin, joint limitation and progressive restriction of chest that may lead to death. We describe the efficacy of haematopoietic autologous stem cell transplantation (HSCT) in a case of SSS secondary to a smouldering myeloma (SM), with severe joint disability, lung interstitial disease and oesophageal dysfunction. The patient was evaluated at 1, 12 and 18 months after HSCT, clinically (joint motility, HAQ and NYHA for dyspnoea) and instrumentally (DLCO, chest HRCT, oesophagus x-ray). After 18 months since HSCT, we observed a high improvement, contemporaneously to SM remission, of HAQ, joint motility, lung (at DLCO and HRCT) and oesophageal abnormalities.

Ultrasound detects occult entheseal involvement in early psoriatic arthritis independently of clinical features and psoriasis severity.

OBJECTIVES: Entheseal involvement is a frequent and distinctive feature of psoriatic arthritis (PsA), and is often under-diagnosed. The aim of the present study is to investigate using ultrasound (US), lower limb entheseal abnormalities in patients with early psoriatic arthritis (ePsA) and to evaluate their correlation with ePsA clinical characteristics. METHODS: Ninety-two ePsA patients (with duration of symptoms less than 1 year), diagnosed according to CASPAR criteria, were consecutively scored with Glasgow Ultrasound Enthesitis Scoring System (GUESS) and Power Doppler (PD) US (My Lab 70 Esaote) of lower limbs entheses (quadriceps, patellar, achilles tendons and plantar fascia). Patients were clinically examined by palpation of lower limbs entheses, Maastricht Ankylosing Spondylitis Enthesitis Index (MASES) and total Psoriasis Area and Severity Index (PASI). Correlations were investigated between GUESS and PD with other ePsA clinical characteristics (duration of symptoms and morning stiffness, pain and fatigue visual analogue scale [VAS], Health Assessment Questionnaire SpA-modified [S-HAQ]). RESULTS: All patients had GUESS>1 and 40.2% showed positive PD signal on entheses, at a higher percentage than tenderness revealed by clinical examination (29.3%). GUESS and PD did not correlate with MASES, PASI and other clinical characteristics. No significant differences in GUESS and PD were detected between positive or negative findings of MASES and PASI. CONCLUSIONS: US detects subclinical entheseal involvement in ePsA, independently of ePsA clinical examination and symptoms.

Post-COVID-19 and Post-COVID-19 Vaccine Arthritis, Polymyalgia Rheumatica and Horton's Arteritis: A Single-Center Assessment of Clinical, Serological, Genetic, and Ultrasonographic Biomarkers.

The potential role of the COVID-19 vaccine and infection to induce autoimmunity is currently underestimated despite the literature emphasizing arthralgia as a common adverse event. We aimed to study the impact of rheumatological complications post-COVID-19 (PC) and post-COVID-19 vaccine (PCV), comparing undifferentiated arthritis (UA) to Polymyalgia Rheumatica, Horton's Arteritis (PMR-HA) and isolated arthritis to UA with "connective-like" accompanying symptoms. We retrospectively included 109 patients with at least 6 months of follow-up, analyzing serum biomarkers, joint ultrasound (US), lung HRCT, DLCO, and HLA haplotypes. There were 87 UA patients showing increased gastrointestinal and lung involvement (p = 0.021 and p = 0.012), higher anti-spike protein IgG levels (p = 0.003), and anti-SARS-CoV-2 IgG positivity (p = 0.003). Among them, 66 cases progressed to ACR-EULAR 2010 early arthritis after 3 months, whereas PMR-HA patients were more commonly PCV (81.8%, p = 0.008), demonstrating higher CRP (p = 0.007) and ESR (p = 0.006) levels, a lower rate of ANA positivity (p = 0.005), and a higher remission rate after six months (p = 0.050). In UA patients, the prevalent HLA was DRB1*11 and C*07 (36.8% and 42.1%). Serum calprotectin, interleukin-6, and C*07 (p = 0.021, 0.041, 0.018) seemed more specific for isolated UA. Conversely, "connective-like" arthritis showed poorer DLCO (p = 0.041) and more frequent US synovitis (p = 0.041). In conclusion, UA is a frequent common PC and PCV complication and may persist over time when compared to PMR-HA.

Correction: Benucci et al. Predicting Loss of Efficacy after Non-Medical Switching: Correlation between Circulating TNF-α Levels and SB4 in Etanercept to SB4 Switchers and Naïve Patients with Rheumatic Disease. J. Pers. Med. 2022, 12, 1174.

The authors wish to make the following correction to this paper [...].